This project is concerned with the importance of hippocampal interneurons to information processing and storage. We have found that high-frequency stimulation of the predominantly inhibitory dentate commissural projection (CP) of the rat leads to lasting changes of inhibition in the dentate gyrus (DG). The feed-forward inhibition evoked by the CP increases, while that evoked by the converging perforant path (PP) decreases. The divergent effects are surprising because the two inputs act through a common (or heavily overlapping) pool of interneurons. The finding suggests that the plasticity of interneurons could be as important for information storage as is that of the excitatory synapses on the projection cells. We propose a series of acute electrophysiological experiments designed to explore the dimensions of synaptic plasticity in the hippocampal inhibitory circuits. This will involve population measures of inhibitory neurotransmission, extracellular recordings of individual interneurons, and intracellular recordings from neurons in a hippocampal slice preparation. We will explore the cellular signals controlling plasticity in the disynaptic inhibitory circuit with NMDA receptor antagonists, and with manipulations of post-synaptic membrane potential. We will also pursue a an unexpected finding from our preliminary data. The robust, prolonged, paired pulse facilitation so characteristic of hippocampal circuits can be eliminated by bicuculline, indicating that inhibitory circuits are suppressid between 50 and 200 msec following a single stimulus in this system. The phenomenon is relevant to the priming effect and it could reflect activity in the septo-hippocampal connections. The results of our project will be relevant to information processing, epileptogenesis, and seizure propagation.